Dock-MD-FEP-solvation.ipynb

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   "source": [
    "# **Dock-MD-FEP-solvation**\n",
    "\n",
    "---\n",
    "Docking, Molecular dynamic(MD), and Free energy perturbation (FEP) are important modelling methods in medicinal chemistry.\n",
    "\n",
    "This Jupyter notebook shows how to run a Three-in-one simulation, i.e., docking, MD and FEP, with freely available GPU(and CPU) from Google Colab.\n",
    "\n",
    "---\n",
    "\n",
    " **This notebook has NOT been thoroughly tested and validated. Use it at your own risk!** \n",
    "\n",
    "--- \n",
    "\n",
    "**This notebook is based on**\n",
    "- The MD simulation is based on [OpenMM](https://openmm.org/) and [Making-it-rain](https://twitter.com/pablitoarantes)\n",
    "\n",
    "- The FEP simulation is based on [Yank](http://getyank.org/latest/)\n",
    "\n",
    "\n",
    "- Other open-soured packages like [Open-Sourced-PyMOL](https://anaconda.org/conda-forge/pymol-open-source)/  [OpenBabel](https://github.com/openbabel/openbabel)/ [Rdkit](https://github.com/rdkit/rdkit) etc.\n",
    "\n",
    "- Also, some github example/tutorial repositories,  [Yank example](https://github.com/choderalab/yank-examples) and [A customized yank script](https://github.com/quantaosun/OpenMM-Yank-YAML-template)\n",
    "\n",
    "- Please use https://github.com/quantaosun/Ambertools-OpenMM-MD to generate a ligand4.mol2 file before moving on.\n",
    "\n"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {
    "id": "2-4G5DKMwl_g",
    "tags": []
   },
   "source": [
    "# Yank Installation (Stage 3)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "metadata": {
    "cellView": "form",
    "id": "aN-GOJywzo03",
    "tags": []
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "/root/Dock-MD-FEP/yank-examples/examples/binding/t4-lysozyme/input\n"
     ]
    }
   ],
   "source": [
    "#@title Download an example from github\n",
    "#!git clone https://github.com/choderalab/yank-examples.git\n",
    "%cd yank-examples/examples/binding/t4-lysozyme/input"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {
    "cellView": "form",
    "id": "4BbnbrJ7zyT9",
    "tags": []
   },
   "outputs": [],
   "source": [
    "#@title Modify the sturcture of this example and Remove old ligand, put inside new ligand\n",
    "%%bash\n",
    "cp ../../../../../ligand.mol2 .\n",
    "mv ligand.tripos.mol2 ligand.tripos.mol2.old\n",
    "mv ligand.mol2 ligand.tripos.mol2"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {
    "cellView": "form",
    "id": "Z4Ov2c812gQt",
    "tags": []
   },
   "outputs": [],
   "source": [
    "#@title Go to working directory\n",
    "%cd .."
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {
    "id": "iHcKHeJcKv2v",
    "tags": []
   },
   "source": [
    "# FEP simulation- Absolute binding free energy of docked Top1 pose (Stage 3)\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {
    "cellView": "form",
    "id": "Y_9sBQ0g17vY",
    "tags": []
   },
   "outputs": [],
   "source": [
    "#@title Download a modified yaml flie for cloud fep\n",
    "!git clone https://github.com/quantaosun/OpenMM-Yank-YAML-template.git"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {
    "cellView": "form",
    "id": "VNsGhsoi2NpR",
    "tags": []
   },
   "outputs": [],
   "source": [
    "#@title Copy the modified yaml file to this working path\n",
    "!cp OpenMM-Yank-YAML-template/implicit-1000_per_iteration_doubled_lambda.yaml ."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {
    "cellView": "form",
    "id": "DFNDY4Cp1emy",
    "tags": []
   },
   "outputs": [],
   "source": [
    "#@title Start FEP simulation\n",
    "!yank script --yaml=implicit-1000_per_iteration_doubled_lambda.yaml"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {
    "cellView": "form",
    "id": "FjfJJHqP-rDD",
    "tags": []
   },
   "outputs": [],
   "source": [
    "#@title Job control to keep browser from being idle.\n",
    "#while True:pass\n"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {
    "id": "fHSb4yq328eR",
    "tags": []
   },
   "source": [
    "# FEP Analysis (Stage 3)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {
    "cellView": "form",
    "id": "t5wic-iZ2sEg",
    "tags": []
   },
   "outputs": [],
   "source": [
    "#@title Install Some packages \n",
    "!conda install -c conda-forge pyyaml=5.4 --yes 2>&1 1>/dev/null\n",
    "!conda install -c conda-forge seaborn --yes 2>&1 1>/dev/null\n",
    "!conda install -c conda-forge matplotlib-base --yes 2>&1 1>/dev/null\n",
    "!conda install -c conda-forge jupyter_core --yes 2>&1 1>/dev/null"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {
    "cellView": "form",
    "id": "gL4xpuf8xRmd",
    "tags": []
   },
   "outputs": [],
   "source": [
    "#@title ΔG calculation.\n",
    "%cd ./p-xylene-implicit-output/\n",
    "!yank analyze --store=./experiments/"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {
    "id": "gSOeJnvYm7Ga",
    "tags": []
   },
   "source": [
    "# FEP Quality Report (Stage 3)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {
    "id": "kV3tgYhVma0s",
    "tags": []
   },
   "outputs": [],
   "source": [
    "!pip install environment_kernels"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {
    "id": "TPVqIIZLmldI",
    "tags": []
   },
   "outputs": [],
   "source": [
    "%rm -r ~/.jupyter"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {
    "cellView": "form",
    "id": "rKqdASm0m2-i",
    "tags": []
   },
   "outputs": [],
   "source": [
    "#@title List a list of package names and version\n",
    "!pip list | grep jupyter | cut -f 1 -d ''|xargs "
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {
    "id": "OnHCUKaC4bUO",
    "tags": []
   },
   "outputs": [],
   "source": [
    "#@title Install a list of packages with certain version\n",
    "!pip install -U --force-reinstall jupyter==1.0.0  jupyter_client==7.3.5 jupyter-console==6.4.4 jupyter_core==4.11.1 jupyterlab-pygments==0.2.2 jupyterlab-widgets==3.0.3"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {
    "id": "vIlQJYBLm3ED",
    "tags": []
   },
   "outputs": [],
   "source": [
    "!jupyter notebook --generate-config"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {
    "id": "YfuBLweXmliv",
    "tags": []
   },
   "outputs": [],
   "source": [
    "!conda install -c conda-forge google-colab --yes"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {
    "id": "-7WVNtuqrPk3",
    "tags": []
   },
   "outputs": [],
   "source": [
    "!jupyter notebook --config=/usr/local/etc/jupyter/jupyter_notebook_config.json"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {
    "cellView": "form",
    "id": "ZNC7r-Chrxer",
    "tags": []
   },
   "outputs": [],
   "source": [
    "#@title Write out report\n",
    "!yank analyze report -s ./experiments/ -o fep_quality.html --format=html"
   ]
  }
 ],
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